Identification and molecular docking study of fish roe-derived peptides as potent BACE 1, AChE, and BChE inhibitors

2020 ◽  
Vol 11 (7) ◽  
pp. 6643-6651 ◽  
Author(s):  
Zhipeng Yu ◽  
Huizhuo Ji ◽  
Juntong Shen ◽  
Ruotong Kan ◽  
Wenzhu Zhao ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Docking ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Beta Secretase ◽  
Fish Roe ◽  
Bace 1

Acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and beta-secretase 1 (BACE 1) play vital roles in the development and progression of Alzheimer's disease (AD).

Identification of Human Acetylcholinesterase Inhibitors from the Constituents of EGb761 by Modeling Docking and Molecular Dynamics Simulations

2018 ◽  
Vol 21 (1) ◽  
pp. 41-49 ◽  
Author(s):  
Lihu Zhang ◽  
Dongdong Li ◽  
Fuliang Cao ◽  
Wei Xiao ◽  
Linguo Zhao ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Docking ◽  
Serine Proteases ◽  
Colorimetric Method ◽  
Acetylcholinesterase Inhibitors ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Ache Inhibitors ◽  
Starting Point

Aim and Objective: EGb761, a standardized and well-defined product extract of Ginkgo biloba leaves, has beneficial role in the treatment of multiple diseases, particularly Alzheimer's disease (AD). Identification of natural acetylcholinesterase (AChE) inhibitors from EGb761 would provide a novel therapeutic approach against the Alzheimer's disease. Material and Method: A series of 21 kinds of promising EGb761 compounds were selected, and subsequently evaluated for their potential ability to bind AChE enzyme by molecular docking and a deep analysis of protein surface pocket features. Results: Docking results indicated that these compounds can bind tightly with the active site of human AChE, with favorable distinct interactions around several important residues Asp74, Leu289, Phe295, Ser293, Tyr341, Trp286 and Val294 in the active pocket. Most EGB761 compounds could form the hydrogen bond interactions with the negatively charged Asp74 and Phe295 residues. Among these compounds, diosmetin is the one with the best-predicted docking score while three key hydrogen bonds can be formed between small molecule and corresponding residues of the binding site. Besides, other three compounds luteolin, apigenin, and isorhamnetin have better predicted docking scores towards AChE than other serine proteases, i.e Elastase, Tryptase, Factor XA, exhibiting specificity for AChE inhibition. The RMSD and MM-GBSA results from molecular dymamic simulations indicated that the docking pose of diosmetin-AChE complex displayed highly stable, which can be used for validating the accuracy of molecular docking study. Subsequently, the AChE inhibitory activities of these compounds were evaluated by the Ellman's colorimetric method. Conclusion: The obtained results revealed that all the four compounds exhibited modest AChE inhibitory activity, among which Diosmetin manifested remarkable anti-AChE activity, comparable with the reference compound, Physostigmine. It can be deduced that these EGB761 compounds can be regarded as a promising starting point for developing AChE inhibitors against AD.

scholarly journals Putative Molecular Mechanisms of Neuroprotective Cerebrosides and Their Docking Studies on Acetyl Cholinesterase Enzyme Inhibition for the Treatment of Alzheimer’s Disease

2021 ◽  
Author(s):  
SHAIK IBRAHIM KHALIVULLA ◽  
Kokkanti Mallikarjuna
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Docking ◽  
Enzyme Inhibition ◽  
Docking Study ◽  
Tau Proteins ◽  
World Health ◽  
Molecular Docking Study ◽  
Ache Inhibitors ◽  
Catalytic Active Site

Abstract The Dementia disease is characterised by neuropsychiatric disturbances due to lack of proper synaptic communication between neurons causing the cognitive behavioural problems. The Alzheimer’s disease (AD) in elderly population is one of the several forms of Dementia. Recent data by World Health Organisation indicates that nearly 10 million people are getting dementia every year, of which 60-70% accounts for AD. The etiology of AD involves the formation of amyloid-β plaques and neurofibrillary Tau tangles in the brain resulting in the death of neural cells. There is no permanent solution for AD treatment, except the FDA approved drugs like galantamine, donepezil, rivastigmine and memantine that are normally associated with side effects. At this juncture, cerebrosides, the natural secondary metabolites identified from different taxa with potential neuroprotective effects offer a promising scope for the treatment of AD. In this paper, cerebrosides reported from all taxa are pooled up along with their functions and listed. The review of literature revealed that Cerebrosides can increase the cognitive functions by regulating or interacting with the N-methyl-d-aspartate (NMDA) calcium ion (Ca2+) channels at post-synaptic receptor; nitric oxide (NO); Bcl2, Bax, amyloid precursor (APP) and Tau proteins; brain-derived neurotrophic factor (BDNF) and cAMP- response element-binding proteins (CREB).This indicates that the Cerebrosides could be potential therapeutic agents for the protection of neurons involved in neurodegenerative disease like Alzheimer’s disease. The current neuroprotective drugs are AChE inhibitors; hence, in the present investigation, in silico molecular docking study on cerebrosides for the inhibition of AChE was assessed to find out their capacity to interact with an active catalytic site of AChE. The results of present investigation revealed that all 22 cerebrosides selected for this work interacted with catalytic active site of AChE measured in terms of Gibbs free binding energy. Of all the cerebrosides assessed, compound 6 exhibited strong interaction, followed by 15. This is the first report of molecular docking study on cerebrosides for AChE enzyme inhibition for treatment of Alzheimer’s disease. Nevertheless, detailed in vitro and in vivo, biochemical and molecular investigations are needed to bring them to useful form.

scholarly journals Halogen-directed drug design for Alzheimer’s disease: a combined density functional and molecular docking study

SpringerPlus ◽  
2016 ◽  
Vol 5 (1) ◽  
Author(s):  
Adhip Rahman ◽  
Mohammad Tuhin Ali ◽  
Mohammad Mahfuz Ali Khan Shawan ◽  
Mohammed Golam Sarwar ◽  
Mohammad A. K. Khan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Docking ◽  
Drug Design ◽  
Density Functional ◽  
Docking Study ◽  
Molecular Docking Study

scholarly journals Computational Exploration of Phytochemicals as Potent Inhibitors of Acetylcholinesterase Enzyme in Alzheimer’s Disease

2020 ◽  
Author(s):  
Bishajit Sarkar ◽  
Md. Asad Ullah ◽  
Md. Nazmul Islam Prottoy
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Docking ◽  
Docking Study ◽  
Dynamics Simulation ◽  
Normal Brain ◽  
Molecular Docking Study ◽  
Brain Functions ◽  
Age Related ◽  
Acetylcholinesterase Enzyme

AbstractAlzheimer’s Disease (AD) is the most common type of age related dementia in the world. Many hypotheses shed light on several reasons that lead to AD development. The cholinergic hypothesis describes that the destruction of an essential neurotransmitter, acetylcholine (AChE) by acetylcholinesterase (AChE) enzyme, leads to the AD onset. The hydrolysis of acetylcholine by excess amount of AChE decreases the amount of acetylcholine in the brain, thus interfering with the normal brain functions. Many anti-AChE agents can be used to treat AD by targeting AChE. In our study, 14 anti-AChE agents from plants: 1,8-cineol, berberine, carvacrol, cheilanthifoline, coptisine, estragole, harmaline, harmine, liriodenine, myrtenal, naringenin, protopine, scoulerine, stylopine were tested against AChE and compared with two controls: donepezil and galantamine, using different techniques of molecular docking. Molecular docking study was conducted for all the 14 selected ligands against AChE to identify the best three ligands among them. To determine the safety and efficacy of the three best ligands, a set of tests like the druglikeness property test, ADME/T test, PASS & P450 site of metabolism prediction, pharmacophore mapping and modelling and DFT calculations were performed. In our experiment, berberine, coptisine and naringenin were determined as the three ligands from the docking study. Further analysis of these 3 ligands showed coptisine as the most potent anti-AChE agent. The molecular dynamics simulation study showed quite good stability of the coptisine-AChE docked complex. Administration of berberine, coptisine and naringenin might be potential treatments for AD.

Spirocyclohexadienones as an Uncommon Scaffold for Acetylcholinesterase Inhibitory Activity

2019 ◽  
Vol 15 (4) ◽  
pp. 373-382 ◽  
Author(s):  
Ralph C. Gomes ◽  
Renata P. Sakata ◽  
Wanda P. Almeida ◽  
Fernando Coelho
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Population Aging ◽  
Acetylcholinesterase Inhibitors ◽  
Acetylcholinesterase Activity ◽  
Docking Study ◽  
Biological Properties ◽  
Ache Inhibitor ◽  
Molecular Docking Study

Background: The most important cause of dementia affecting elderly people is the Alzheimer’s disease (AD). Patients affected by this progressive and neurodegenerative disease have severe memory and cognitive function impairments. Some medicines used for treating this disease in the early stages are based on inhibition of acetylcholinesterase. Population aging should contribute to increase the cases of patients suffering from Alzheimer's disease, thus requiring the development of new therapeutic entities for the treatment of this disease. Methods: The objective of this work is to identify new substances that have spatial structural similarity with donepezil, an efficient commercial drug used for the treatment of Alzheimer's disease, and to evaluate the capacity of inhibition of these new substances against the enzyme acetylcholinesterase. Results: Based on a previous results of our group, we prepared a set of 11 spirocyclohexadienones with different substitutions patterns in three steps and overall yield of up to 59%. These compounds were evaluated in vitro against acetylcholinesterase. We found that eight of them are able to inhibit the acetylcholinesterase activity, with IC50 values ranging from 0.12 to 12.67 µM. Molecular docking study indicated that the spirocyclohexadienone, 9e (IC50 = 0.12 µM), a mixedtype AChE inhibitor, showed a good interaction at active site of the enzyme, including the cationic (CAS) and the peripheral site (PAS). Conclusion: We described the first study aimed at investigating the biological properties of spirocyclohexadienones as acetylcholinesterase inhibitors. Thus, we have identified an inhibitor, which provided valuable insights for further studies aimed at the discovery of more potent acetylcholinesterase inhibitors.

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